This 5-year K07 award application is designed to provide the applicant, whose formal training has been in clinical psychology, with the mentoring and "protected" time to pursue multidisciplinary research training spanning basic biology, genetics, behavioral sciences, epidemiology, and biostatistics. At the end of this training, the applicant will have developed sufficient expertise to be a fully established, independent investigator at the forefront of research exploring the biobehavioral links between genetic factors and smoking behavior. The proposed training includes both formal and informal didactics, as well as a complementary program of innovative research. Didactics will include completion of an MPH degree, other selected graduate course work in biology, and informal colloquia. The research project, which explores genetic factors in persistent smoking, will serve as a hands-on model of biobehavioral investigations of clinically relevant hypotheses grounded in the basic sciences. Most smokers express a strong interest in quitting, but only a small minority are successful. Accumulating evidence suggests that genetic factors play a role in this persistent smoking. In particular, research has demonstrated that smokers who carry specific polymorphisms that confer increased sensitivity to dopamine have higher levels of persistent smoking behavior. The underlying biobehavioral mechanisms linking these polymorphisms to persistent smoking are not yet known. Based on several independent lines of research, we propose to test the possibility that smokers with these polymorphisms display greater craving reactions to specific smoking cues, and perhaps appetitive cues generally, than smokers without, which may account for their higher levels of persistent smoking. To that end, a 4 year, laboratory-based study with 448 smokers (50 percent male, 50 percent female), is proposed. These healthy participants will be tested for specific polymorphisms, and their reactions to smoking cues, chocolate cues, and neutral cues will be assessed by self report and cardiovascular monitoring. In addition, they will complete questionnaires about their smoking patterns. Statistical analyses will examine relations between genetype, cue reactivity, and persistent smoking, behavior. Based on the results et that study, the applicant will begin developing and pilot testing interventions to reduce heightened reactivity among smokers with genetic vulnerability. The award is viewed as instrumental to the applicant in achieving his short-term goal of becoming an independent biobehavioral cancer control researcher, as well as his longer-term objective- to "bridge the gap" between the basic sciences and clinical applications by becoming competent in developing and testing clinically relevant "multidisciplinary" hypotheses informed by the basic biological and biobehavioral sciences.